Partial agonist activity of celiprolol as assessed in conscious unrestrained dogs in comparison with those of pindolol and labetalol.

The effects of celiprolol on the heart rate (HR) and the total peripheral resistance (TPR) were studied in chronically instrumented conscious dogs in comparison with those of pindolol, propranolol and labetalol. Intravenous injection of pindolol, celiprolol and labetalol increased the HR and decreased the TPR dose-dependently, whereas propranolol did not. The ratios of doses that elicited 12% changes in both parameters (HR12/TPR12) were 4.85 +/- 2.63, 0.61 +/- 0.03 and 0.42 +/- 0.11 for celiprolol, pindolol and labetalol, respectively, indicating the preferential reduction of TPR by celiprolol. Changes in HR and TPR produced by these three agents were antagonized by propranolol dose-dependently. However, inhibition by 3 mg/kg of propranolol was incomplete in the cases of labetalol-induced decrease in the TPR at the dose of TPR12 (51%) and celiprolol-induced increase in the HR at the dose of HR12 (89%). These results suggest that changes produced by celiprolol as well as pindolol and labetalol were mostly explainable by partial agonist activity via beta-adrenoceptors. However, the contribution of the alpha-blocking activity must also be taken into consideration in the case of the reduction of the TPR by labetalol. In addition, there is a possibility that celiprolol may increase HR via its direct action.